Epitope-specific IgG pools identify PfCRT monomer and homodimer polypeptides that are differentially phosphorylated at Ser411 in Plasmodium falciparum

2021 ◽  
Vol 557 ◽  
pp. 261-266
Author(s):  
Fadi Baakdah ◽  
Elias Georges
Keyword(s):  
Plasmodium Falciparum ◽  
Specific Igg

scholarly journals Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mads Delbo Larsen ◽  
Mary Lopez-Perez ◽  
Emmanuel Kakra Dickson ◽  
Paulina Ampomah ◽  
Nicaise Tuikue Ndam ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Nk Cell ◽  
Antibody Responses ◽  
Central Component ◽  
Dependent Manner ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Enveloped Viruses ◽  
A Subunit ◽  
Specific Igg ◽  
Induced Immunity

AbstractPlasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members mediate receptor- and tissue-specific sequestration of infected erythrocytes (IEs) in malaria. Antibody responses are a central component of naturally acquired malaria immunity. PfEMP1-specific IgG likely protects by inhibiting IE sequestration and through IgG-Fc Receptor (FcγR) mediated phagocytosis and killing of antibody-opsonized IEs. The affinity of afucosylated IgG to FcγRIIIa is up to 40-fold higher than fucosylated IgG, resulting in enhanced antibody-dependent cellular cytotoxicity. Most IgG in plasma is fully fucosylated, but afucosylated IgG is elicited in response to enveloped viruses and to paternal alloantigens during pregnancy. Here we show that naturally acquired PfEMP1-specific IgG is strongly afucosylated in a stable and exposure-dependent manner, and efficiently induces FcγRIIIa-dependent natural killer (NK) cell degranulation. In contrast, immunization with a subunit PfEMP1 (VAR2CSA) vaccine results in fully fucosylated specific IgG. These results have implications for understanding protective natural- and vaccine-induced immunity to malaria.

scholarly journals Geographical and Temporal Conservation of Antibody Recognition of Plasmodium falciparum Variant Surface Antigens

2004 ◽  
Vol 72 (6) ◽  
pp. 3531-3535 ◽  
Author(s):  
Morten A. Nielsen ◽  
Lasse S. Vestergaard ◽  
John Lusingu ◽  
Jørgen A. L. Kurtzhals ◽  
Haider A. Giha ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Protective Immunity ◽  
Surface Antigens ◽  
African Countries ◽  
Variant Surface Antigens ◽  
Antibody Recognition ◽  
Specific Immunoglobulin ◽  
Life Threatening ◽  
Specific Igg ◽  
Plasma Collection

ABSTRACT The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.

Schistosoma haematobium infection affects Plasmodium falciparum-specific IgG responses associated with protection against malaria

2011 ◽  
Vol 33 (2) ◽  
pp. 124-131 ◽  
Author(s):  
D. COURTIN ◽  
A. DJILALI-SAÏAH ◽  
J. MILET ◽  
V. SOULARD ◽  
O. GAYE ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Schistosoma Haematobium ◽  
Specific Igg

Variant surface antigen-specific IgG and protection against clinical consequences of pregnancy-associated Plasmodium falciparum malaria

The Lancet ◽  
2004 ◽  
Vol 363 (9405) ◽  
pp. 283-289 ◽  
Author(s):  
Trine Staalsoe ◽  
Caroline E Shulman ◽  
Judith N Bulmer ◽  
Ken Kawuondo ◽  
Kevin Marsh ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Surface Antigen ◽  
Plasmodium Falciparum Malaria ◽  
Variant Surface Antigen ◽  
Clinical Consequences ◽  
Specific Igg

scholarly journals A comparative analysis of memory B cell and antibody responses against Plasmodium falciparum merozoite surface protein 1 in children and adults from Uganda

2021 ◽  
Author(s):  
S Jake Gonzales ◽  
Kathleen N Clarke ◽  
Gayani Batugedara ◽  
Ashley E Braddom ◽  
Rolando Garza ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
B Cells ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Antibody Responses ◽  
Amino Acid Substitutions ◽  
Humoral Immune ◽  
Merozoite Surface Protein 1 ◽  
Specific Igg

Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against P. falciparum develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, merozoite surface protein 1 (MSP1), in individuals from a region in Uganda with high P. falciparum transmission. Our results showed that MSP1-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ MSP1-specific classical MBCs. In contrast, anti-MSP1 plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against MSP1 and whole merozoites, with broadening of the response against non-3D7 strains in adults. The antibodies encoded by MSP1-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable MSP1 protein. Proteomics analysis of MSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to MSP1-specific MBCs, anti-MSP1 IgGs had relatively high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the MSP1-specific humoral immune response with cumulative P. falciparum exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of MSP1 variants by the plasma IgG repertoire.

scholarly journals Baculovirus-Expressed Constructs Induce Immunoglobulin G That Recognizes VAR2CSA on Plasmodium falciparum- Infected Erythrocytes

2006 ◽  
Vol 74 (7) ◽  
pp. 4357-4360 ◽  
Author(s):  
Lea Barfod ◽  
Morten A. Nielsen ◽  
Louise Turner ◽  
Madeleine Dahlbäck ◽  
Anja T. R. Jensen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Plasmodium Falciparum ◽  
Immunosorbent Assay ◽  
Immunoglobulin G ◽  
Insect Cell ◽  
Insect Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specific Antisera ◽  
Specific Igg

ABSTRACT We raised specific antisera against recombinant VAR2CSA domains produced in Escherichia coli and in insect cells. All were reactive in enzyme-linked immunosorbent assay, but only insect cell-derived constructs induced immunoglobulin G (IgG) that was reactive with native VAR2CSA on the surface of infected erythrocytes. Our data show that five of the six VAR2CSA Duffy-binding-like domains are surface exposed and that induction of surface-reactive VAR2CSA-specific IgG depends critically upon antigen conformation. These findings have implications for the development of vaccines against pregnancy-associated Plasmodium falciparum malaria.

Analysis of Plasmodium falciparum infections in a village community in Northern Nigeria: determination of msp2 genotypes and parasite-specific IgG responses

Acta Tropica ◽  
2000 ◽  
Vol 74 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Fred Engelbrecht ◽  
Eva Tögel ◽  
Hans-Peter Beck ◽  
Felicia Enwezor ◽  
Annelies Oettli ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Northern Nigeria ◽  
Village Community ◽  
Specific Igg

scholarly journals Plasmodium falciparum VAR2CSA-Specific IgG Subclass Responses Reflect Protection Against Low Birth Weight and Pregnancy-Associated Malaria

2021 ◽  
Vol 12 ◽  
Author(s):  
Bernard Tornyigah ◽  
Tania d’Almeida ◽  
Guillaume Escriou ◽  
Firmine Viwami ◽  
Nadine Fievet ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Pregnancy Outcomes ◽  
Placental Malaria ◽  
Vaccine Antigen ◽  
Igg Subclass ◽  
Malaria Vaccines ◽  
Immunological Mechanisms ◽  
Specific Igg

Sequestration of Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen in the placenta results in poor pregnancy outcomes, including low birth weight and maternal anemia. Antigen-specific antibody-mediated immunity is acquired during successive pregnancies. Thus, evaluating VAR2CSA-specific IgG profiles among pregnant women will increase knowledge on the immunological mechanisms associated with protection, and help in the development of VAR2CSA-based placental malaria vaccines. Using the PAMVAC candidate vaccine antigen, we assessed anti-VAR2CSA IgG subclass responses of a cohort of pregnant Beninese, and analyzed their relationships with pregnancy outcomes. Cytophilic IgG1 and IgG3 responses were the most frequent, with prevalences ranging from 28% (IgG3) up to 50% (IgG1). Elevated levels of VAR2CSA-specific total IgG and cytophilic IgG3 during pregnancy were consistently associated with higher birth weights, whilst high levels of IgG4 were associated with a reduced risk of placental infections. This suggests that protective anti-VAR2CSA IgG responses are coordinated between both cytophilic and non-cytophilic antibodies.

scholarly journals Plasmodium falciparum–specific IgM B cells dominate in children, expand with malaria, and produce functional IgM

2021 ◽  
Vol 218 (4) ◽  
Author(s):  
Christine S. Hopp ◽  
Padmapriya Sekar ◽  
Ababacar Diouf ◽  
Kazutoyo Miura ◽  
Kristin Boswell ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
B Cells ◽  
Cell Receptor ◽  
Memory B Cells ◽  
B Cell Receptor ◽  
Longitudinal Analyses ◽  
Igg Antibodies ◽  
Specific Memory ◽  
Specific Igg

IgG antibodies play a role in malaria immunity, but whether and how IgM protects from malaria and the biology of Plasmodium falciparum (Pf)–specific IgM B cells is unclear. In a Mali cohort spanning infants to adults, we conducted longitudinal analyses of Pf- and influenza-specific B cells. We found that Pf-specific memory B cells (MBCs) are disproportionally IgM+ and only gradually shift to IgG+ with age, in contrast to influenza-specific MBCs that are predominantly IgG+ from infancy to adulthood. B cell receptor analysis showed Pf-specific IgM MBCs are somatically hypermutated at levels comparable to influenza-specific IgG B cells. During acute malaria, Pf-specific IgM B cells expand and upregulate activation/costimulatory markers. Finally, plasma IgM was comparable to IgG in inhibiting Pf growth and enhancing phagocytosis of Pf by monocytes in vitro. Thus, somatically hypermutated Pf-specific IgM MBCs dominate in children, expand and activate during malaria, and produce IgM that inhibits Pf through neutralization and opsonic phagocytosis.

scholarly journals Natural and Vaccine-Induced Acquisition of Cross-Reactive IgG-Inhibiting ICAM-1-Specific Binding of a Plasmodium falciparum PfEMP1 Subtype Associated Specifically with Cerebral Malaria

2018 ◽  
Vol 86 (4) ◽  
Author(s):  
Rebecca W. Olsen ◽  
Gertrude Ecklu-Mensah ◽  
Anja Bengtsson ◽  
Michael F. Ofori ◽  
John P. A. Lusingu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cerebral Malaria ◽  
Specific Binding ◽  
Intercellular Adhesion Molecule ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intercellular Adhesion Molecule 1 ◽  
Content Type ◽  
Protein Receptor ◽  
Specific Igg

ABSTRACT Cerebral malaria (CM) is a potentially deadly outcome of Plasmodium falciparum malaria that is precipitated by sequestration of infected erythrocytes (IEs) in the brain. The adhesion of IEs to brain endothelial cells is mediated by a subtype of parasite-encoded erythrocyte membrane protein 1 (PfEMP1) that facilitates dual binding to host intercellular adhesion molecule 1 (ICAM-1) and endothelial protein receptor C (EPCR). The PfEMP1 subtype is characterized by the presence of a particular motif (DBLβ_motif) in the constituent ICAM-1-binding DBLβ domain. The rate of natural acquisition of DBLβ_motif-specific IgG antibodies and the ability to induce such antibodies by vaccination are unknown, and the aim of this study was to provide such data. We used an enzyme-linked immunosorbent assay (ELISA) to measure DBLβ-specific IgG in plasma from Ghanaian children with malaria. The ability of human immune plasma and DBLβ-specific rat antisera to inhibit the interaction between ICAM-1 and DBLβ was assessed using ELISA and in vitro assays of IE adhesion under flow. The acquisition of DBLβ_motif-specific IgG coincided with age-specific susceptibility to CM. Broadly cross-reactive antibodies inhibiting the interaction between ICAM-1 and DBLβ_motif domains were detectable in immune plasma and in sera of rats immunized with specific DBLβ_motif antigens. Importantly, antibodies against the DBLβ_motif inhibited ICAM-1-specific in vitro adhesion of erythrocytes infected by four of five P. falciparum isolates from cerebral malaria patients. We conclude that natural exposure to P. falciparum as well as immunization with specific DBLβ_motif antigens can induce cross-reactive antibodies that inhibit the interaction between ICAM-1 and a broad range of DBLβ_motif domains. These findings raise hope that a vaccine designed specifically to prevent CM is feasible.

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